Molecular Medicine最新文献

{"title":"4-Octyl itaconate alleviates endothelial cell inflammation and barrier dysfunction in LPS-induced sepsis via modulating TLR4/MAPK/NF-κB signaling : 4-Octyl itaconate alleviates endothelial dysfunction.","authors":"Rong Li, Yu Ma, Haoran Wu, Xiao Zhang, Nianhui Ding, Zhichao Li, Xin Hu, Jiajia Rao, Yiting Zhou, Liqun Wang, Ying Wan, Yan Yang, Jianbo Wu, Xiaoqin Zhang, Chunxiang Zhang","doi":"10.1186/s10020-025-01160-2","DOIUrl":"10.1186/s10020-025-01160-2","url":null,"abstract":"<p><strong>Aim: </strong>Sepsis-induced vascular injury is a major contributor to the high mortality rate of sepsis. However, effective treatments remain elusive due to limited knowledge regarding the underlying molecular mechanisms. Itaconic acid, an endogenous metabolite, involved in multiple inflammatory diseases, but its role in sepsis-induced vascular injury remains unclear. The current study investigates the effect of 4-octyl itaconate (4-OI), a cell-permeable derivative of itaconic acid, on sepsis-induced vascular injury and organ damage.</p><p><strong>Methods and results: </strong>An in vitro cell model was established by treating human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) revealed that 4-OI inhibited the LPS-induced increases in TNF-α, IL-6, and IL-1β levels. Cellular reactive oxygen species (ROS) levels, measured using the fluorescent probe DCFH-DA, mitochondrial ROS (mtROS) levels, measured by MitoSOX, and mitochondrial membrane potential (ΔΨ), detected by the fluorescent indicator JC-1, were all reduced following 4-OI treatment. Additionally, mtDNA release, detected by qRT-PCR, were decreased. Mitochondrial morphology, assessed by PK Mito Orange, was preserved by 4-OI treatment. Furthermore, 4-OI suppressed HUVECs apoptosis and pyroptosis, as detected by TUNEL staining and western blotting. 4-OI treatment also significantly inhibited LPS-induced cell adhesion, as shown in THP-1 attachment assay, by decreasing ICAM-1 and VCAM-1 expression. Cell permeability, determined by FITC-Dx-70 leakage, revealed that 4-OI effectively suppressed LPS-induced increases in cell permeability. Furthermore, 4-OI inhibited LPS-induced phosphorylation and internalization of VE-cadherin protein, preserving the adhesion junctions between endothelial cells. Network pharmacology and molecular docking analysis suggested the involvement of TLR4/MAPK/NF-κB signaling pathway as a key mechanism by which 4-OI ameliorated sepsis-induced vascular cell inflammation and injury, which was confirmed by western blotting. The in vitro results were subsequently verified in vivo in an LPS-induced sepsis mouse model. 4-OI pretreatment substantially decreased inflammatory cytokine levels in serum and lung tissues, inhibited pulmonary oedema and pulmonary vascular leakage, as evidenced by the wet-to-dry weight ratio and Evans blue staining of lung tissues, and alleviated tissue damage, as shown by histological analysis. Survival analysis indicated that 4-OI post-sepsis treatment improved the overall survival rate in LPS-induced ALI mice.</p><p><strong>Conclusion: </strong>4-OI protects against sepsis-induced vascular injury and tissue damage by suppressing endothelial inflammation, oxidative stress, and preserving endothelial barrier integrity.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"240"},"PeriodicalIF":6.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALDOC and PGK1 coordinately induce glucose metabolism reprogramming and promote development of colorectal cancer.","authors":"Liyong Huang, Yixin Tong, Xu Li, Wei Wang, Zhen Wang, Bingchen Chen, Jifu E, Ruzhen Zhou, Hantao Wang, Jinghu He","doi":"10.1186/s10020-025-01252-z","DOIUrl":"10.1186/s10020-025-01252-z","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a significant health challenge globally, demanding a comprehensive understanding of its molecular underpinnings for effective management. In this study, we investigated the role of Aldolase C (ALDOC), a glycolytic enzyme, in CRC pathogenesis. Transcriptomic analysis of CRC tissues from The Cancer Genome Atlas (TCGA) revealed a substantial upregulation of ALDOC, correlating with adverse clinical outcomes. Immunohistochemical (IHC) staining of locally collected patient-derived tissues corroborated these findings, demonstrating elevated ALDOC expression in tumor tissues, particularly in advanced stages. Functional studies elucidated the regulatory role of ALDOC in CRC cell phenotypes. ALDOC knockdown significantly inhibited cell proliferation, induced apoptosis, arrested cell cycle progression, and suppressed cell migration in vitro. Moreover, in vivo studies using xenograft models confirmed that ALDOC knockdown attenuated tumor growth. Mechanistically, ALDOC was found to interact with hypoxia-inducible factor 1 alpha (HIF1A) and enhance its transcriptional activity on phosphoglycerate kinase 1 (PGK1), a key glycolytic enzyme. Dual-luciferase reporter assays and chromatin immunoprecipitation experiments validated the ALDOC-mediated transcriptional activation of PGK1. Further functional rescue experiments revealed a synergistic interplay between ALDOC and PGK1 in regulating CRC cell phenotypes. Additionally, ALDOC was implicated in promoting aerobic glycolysis in CRC cells, potentially through PGK1 regulation. Collectively, our findings unveil ALDOC as a critical regulator of CRC pathogenesis, offering insights into its potential as a therapeutic target and highlighting the ALDOC/PGK1 axis as a promising avenue for further investigation in CRC.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"239"},"PeriodicalIF":6.0,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquitin-specific protease 38 modulates atrial fibrillation susceptibility in chronic kidney disease via STRAP stabilization and activation of TGF-β/SMAD signaling.","authors":"Hong Meng, Zongze Qu, Zheng Xiao, Bin Kong, Hongjie Yang, Wei Shuai, He Huang","doi":"10.1186/s10020-025-01296-1","DOIUrl":"10.1186/s10020-025-01296-1","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to elucidate the role of the deubiquitinase USP38 in chronic kidney disease (CKD)-associated atrial fibrillation (AF) by investigating its impact on atrial structural and electrical remodeling and its interaction with STRAP and TGF-β/SMAD signaling.</p><p><strong>Methods: </strong>A murine CKD model was established using a two-stage 5/6 nephrectomy. Cardiomyocyte-specific USP38 knockout (USP38-CKO) and overexpression (USP38-TG) mice were generated. Atrial remodeling, electrophysiological parameters, and fibrosis markers were assessed by echocardiography, histology, and immunoblotting. In parallel, HL-1 cells were treated with indoxyl sulfate (100 μM) and subjected to adenoviral-mediated USP38 modulation. Molecular interactions between USP38 and STRAP were evaluated using immunofluorescence, co-immunoprecipitation, and ubiquitination assays. STRAP knockdown studies further validated the downstream effects of USP38.</p><p><strong>Results: </strong>CKD induced significant upregulation of USP38 in atrial tissue and HL-1 cells. USP38-CKO attenuated atrial fibrosis and reduced collagen I/III and α-SMA expression, whereas USP38-TG exacerbated these effects. Notably, USP38 modulation did not significantly alter atrial effective refractory period, suggesting its primary involvement in structural rather than direct electrical remodeling. Mechanistic studies revealed that USP38 stabilizes STRAP via deubiquitination, thereby enhancing TGF-β/SMAD signaling. STRAP knockdown reversed the pro-fibrotic and arrhythmogenic effects induced by USP38 overexpression.</p><p><strong>Conclusion: </strong>USP38 is a critical mediator of CKD-associated AF, promoting atrial fibrosis and electrical remodeling via STRAP stabilization and TGF-β/SMAD pathway activation. Targeting USP38 may represent a novel therapeutic strategy for CKD-associated AF.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"238"},"PeriodicalIF":6.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reciprocal METTL3-PAX5 regulation in maintaining B-cell identity and promoting B-cell hyperreactivity in SLE.","authors":"Yiying Yang, Ying Zhang, Shasha Xie, Ke Liu, Meidong Liu, Yisha Li, Hui Luo, Xiaoxia Zuo, Huali Zhang, Muyao Guo","doi":"10.1186/s10020-025-01295-2","DOIUrl":"10.1186/s10020-025-01295-2","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"236"},"PeriodicalIF":6.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine production of mononuclear leukocytes in response to respiratory syncytial virus is increased in COPD but suppressed in non-COPD tobacco smokers.","authors":"Sarah D Yanik, Kaschin Jamal Jameel, Simon Rohde, Paul Bürger, Eike Bülthoff, Thomas Grunwald, Juliane Kronsbein, Andrea Koch, Michael R Edwards, Matthias Tenbusch, Jürgen Knobloch","doi":"10.1186/s10020-025-01277-4","DOIUrl":"10.1186/s10020-025-01277-4","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"237"},"PeriodicalIF":6.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PELI2 inhibits colorectal cancer development through MAPK signaling pathway.","authors":"Jialin Liu, Shengyun Hu, Liangbo Zhao, Yanmei Yang, Guanghua Wu, Yimeng Duan, Xinrui Ma, Peiwen Wang, Zhiyong Zhang, Hong Zong","doi":"10.1186/s10020-025-01294-3","DOIUrl":"10.1186/s10020-025-01294-3","url":null,"abstract":"<p><p>Colorectal cancer is one of the most common malignant tumors worldwide. Colorectal cancer has a poor survival rate because it tends to metastasise to the liver and other organs. PELI2, an E3 ubiquitin ligase, is down-expressed in a variety of tumors. However, the role of PELI2 in colorectal cancer has not been revealed. In the present study, we found that expression level of PELI2 were reduced significantly in colorectal tumors compared with normal tissues. Patients with low level of PELI2 expression tended to have poor prognosis. Moreover, PELI2 decreased the proliferation, migration and anti-apoptosis of colorectal cancer cells in vitro. We also constructed xenograft tumor model to verify colorectal tumor growth slowed down after PELI2 overexpression. Transcriptome analysis suggested that PELI2 suppressed colorectal cancer progression via the MAPK signaling pathway. In brief, our study shows that PELI2 inhibits colorectal cancer development by MAPK signaling pathway.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"235"},"PeriodicalIF":6.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AREG⁺ regulatory T cells mediating myocardial repair and neovascularization after myocardial infarction.","authors":"Yan Wang, Jiao Li, Yu Zhang, Pingping He, Weiwei Liu, Weirong Zeng, Chaofu Li, Yixuan Gao, Yongchao Zhao, Changyin Shen, Wenming Chen, Yunhang Li, Ranzun Zhao, Bei Shi","doi":"10.1186/s10020-025-01281-8","DOIUrl":"10.1186/s10020-025-01281-8","url":null,"abstract":"","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"229"},"PeriodicalIF":6.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bavachin ameliorates cisplatin-induced nephrotoxicity by enhancing mitochondrial β-oxidation and lipid metabolism through MFN2.","authors":"Shilu Luo, Ming Yang, Na Jiang, Chenrui Li, Yan Liu, Lin Sun","doi":"10.1186/s10020-025-01283-6","DOIUrl":"10.1186/s10020-025-01283-6","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin-induced nephrotoxicity is a critical adverse reaction that restricts the clinical utilization of cisplatin. Alterations in fatty acid metabolism have been associated with the pathogenesis of cisplatin-induced nephrotoxicity, yet the precise mechanisms remain unclear. Bavachin, a natural flavonoid, exhibits anti-inflammatory, antioxidant, and lipid metabolism-regulating properties, yet its role in mitigating cisplatin-induced nephrotoxicity via mitochondrial β-oxidation remains unexplored. Mitofusin-2 (MFN2), a mitochondrial fusion protein, has emerged as a critical regulator of fatty acid oxidation (FAO) and lipid homeostasis. However, its role in cisplatin-induced nephrotoxicity has not been fully explored.</p><p><strong>Methods: </strong>C57/6L mice were randomly divided into control, DMSO, cisplatin, and cisplatin + Bavachin groups. Blood urea nitrogen (BUN), serum creatinine (SCr), reactive-oxygen-species (ROS), lipid accumulation, and apoptosis were assessed. In vitro, the human proximal tubule epithelial cell line (HK-2) cells were treated with 20 µM cisplatin with or without bavachin. ROS production was detected by the DCFH-DA, lipid deposition was detected by oil red O staining, and MFN2, carnitine palmitoyltransferase 1a (CPT1a) were detected by Western blot (WB).</p><p><strong>Results: </strong>Compared with the cisplatin group, bavachin treatment reduced BUN (21.8%) and SCr (78.7%) in the cisplatin group, accompanied by improvements in renal pathological changes, lipid deposition, and apoptosis. In addition, bavachin up-regulated the expression of MFN2 and CPT1a, while decreasing the cisplatin-induced ROS overproduction. Similar results were found in vitro. Notably, the mitochondrial FAO has been increased in HK-2 cells treated with bavachin. Further, MFN2 siRNA partially reversed these protective effects, accompanied by decreased CPT1a expression and exacerbated lipid deposition.</p><p><strong>Conclusions: </strong>This study is the first to confirm MFN2 as a target for renal protection by bavachin. Mechanistically, Bavachin alleviated cisplatin-induced lipid accumulation and apoptosis by upregulating MFN2 expression, which activated CPT1a to promote mitochondrial FAO. These results will provide a new strategy for cisplatin-based cancer therapy and the reduction of its nephrotoxicity.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"234"},"PeriodicalIF":6.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12160371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ONECUT2 reprograms neuroendocrine fate and is an actionable therapeutic target in small cell lung cancer.","authors":"Mirian Gutiérrez, Irene Zamora, Raquel Iriarte, María José Pajares, Qian Yang, Chen Qian, Nerea Otegui, Joaquín Fernández-Irigoyen, Enrique Santamaría, Nicolas Alcala, Alexandra Sexton-Oates, Lynnette Fernández-Cuesta, Miguel Barajas, Alfonso Calvo, Luis M Montuenga, Beatrice Knudsen, Sungyong You, Michael R Freeman, Ignacio Encío, Mirja Rotinen","doi":"10.1186/s10020-025-01267-6","DOIUrl":"10.1186/s10020-025-01267-6","url":null,"abstract":"<p><p>Small cell lung cancer (SCLC) is a highly aggressive malignancy with extremely poor prognosis. SCLC cells exhibit high plasticity and can progress from neuroendocrine (NE) to non-NE phenotypes. This dynamic evolution promotes treatment resistance and relapses, representing a challenge for targeted therapies in this elusive disease. Here we identify the transcription factor ONECUT2 (OC2) as a driver of plasticity in SCLC, leading to non-NE transcriptional states. OC2 is highly expressed in SCLC tumors compared to normal lung tissue and its expression is associated with heightened clinical stage and lymph node metastasis. We show that OC2 is a repressor of ASCL1, the NE master regulator transcription factor. In addition, OC2 upregulates non-NE programs through activation of c-MYC and Notch signaling. We also demonstrate that OC2 is required for growth and survival of SCLC cells and that it can be targeted with a small molecule inhibitor that acts synergistically with the standard combination of cisplatin and etoposide, providing a novel therapeutic strategy for OC2 active SCLC tumors.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"232"},"PeriodicalIF":6.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Celastrol improves endothelial function in diet-induced obesity mice via attenuating endoplasmic reticulum stress through the activation of AMPK pathway.","authors":"Cheng Yu, Weihong Lin, Jing Yang, Qiong Jiang, Wenkun Liu, Hongjin Liu, Yong Lin, Litao Wang, Lei Chen, Yu Huang, Lianglong Chen","doi":"10.1186/s10020-025-01259-6","DOIUrl":"10.1186/s10020-025-01259-6","url":null,"abstract":"<p><strong>Background: </strong>Diet-induced obesity (DIO) is a significant factor in endothelial dysfunction. Celastrol, a potent anti-inflammatory and anti-oxidative pentacyclic triterpene, has shown promise as a protective agent against cardiovascular disease. However, the specific protective effects and mechanisms of celastrol in preventing endothelial dysfunction in diet-induced obesity are not yet fully understood.</p><p><strong>Methods and results: </strong>In this study, eight-week-old C57BL/6 mice were fed a normal or high-fat diet and treated with or without celastrol for 8 weeks. We measured acetylcholine-induced endothelium-dependent relaxation (EDR) in the aortae using a wire myograph. The results revealed that EDR was impaired in DIO mice, along with decreased AMPK phosphorylation, increased endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS) in the aortae. These effects were reversed by celastrol treatment. Celastrol also reversed tunicamycin-induced ER stress, decreased nitric oxide (NO) production, and impaired EDR in mouse aortae. The protective effects of celastrol were negated by co-treatment with an AMPK inhibitor (Compound C). Furthermore, in AMPKα deficient mice, the beneficial effects of celastrol on EDR were significantly reduced.</p><p><strong>Conclusions: </strong>These findings suggest that celastrol improves endothelial function by inhibiting ER stress and increasing NO production through the activation of the AMPK pathway in DIO mice.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"233"},"PeriodicalIF":6.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}